Ischemia-reperfusion injury is a well known occurring pathologic condition. It may either represent a foreseen pathologic condition or an unforeseen pathologic condition. Stroke is one of the most common types of unforeseen ischemia-reperfusion injury. Stroke is the third cause of death and the leading cause of long-term disability in industrialized countries. Stroke is a type of cardiovascular disease that affects the arteries leading to and within the brain. A stroke occurs when such arteries are blocked by a clot or bursts and results in ischemia of the cerebral tissues that are served by the blocked artery. Direct damage to the brain is caused by the interruption of the blood flow, mainly due to loss of oxygenation to the viable tissue, ultimately leading to infarction if not reversed. However if the insult is reversed (either physiologically or therapeutically) then reperfusion of the ischemic tissue may paradoxically cause further indirect damage. When there is a long duration of ischemia, the “direct” damage resulting from hypoxia alone is the predominant mechanism. For shorter duration's of ischemia, the indirect or reperfusion mediated damage becomes increasingly more important to the final outcome.
C1 inhibitor (C1INH), the inhibitor of complement C1, has been reported to display neuro-protective action by reducing ischemia-reperfusion injury in rodent models for cerebral ischemia-reperfusion. (De Simoni et al., 2003, J Cereb Blood Flow Metab. 23: 232-9; Akita et al., 2003, Neurosurgery 52: 395-400). The neuro-protective action of C1INH on brain ischemia-reperfusion injury does not require C1q (De Simoni et al., 2004, Am J Pathol. 164: 1857-63). More recently Storini et al. (2005, Neurobiol Dis. 19: 10-7) reported that C1INH exerts an anti-inflammatory and anti-apoptotic action on ischemia-reperfusion injury through inhibition of inflammation and cell recruitment from the vasculature to the ischemic site. However, the window in time around the stroke during which administration of C1INH is therapeutically effective is rather narrow. It is therefore an object of the present invention to provide for C1INH with a broader window in terms of time of administration.